Fluorene-induced stress in the benthic oligochaete Tubifex tubifex: A multi-biomarker assessment of toxicological pathways and mechanisms under acute and subchronic exposures.

This study examined the multifaceted impacts of fluorene exposure on Tubifex tubifex, encompassing acute (survival analysis and behavioral responses) and subchronic exposure regimens (antioxidant enzyme response and histopathology), molecular docking studies, and generalized read-across analysis. Survival analysis revealed concentration-dependent increases in toxicity over varying time intervals, with LC50 values decreasing from 30.072 mg/L at 24 h to 12.365 mg/L at 96 h, emphasizing the time-sensitive and concentration-responsive nature of the stressor. Behavioral responses were both concentration- and duration-dependent. While Erratic Movement and Clumping Tendency exhibited earlier responses (within 24 h) at lower concentrations, the wrinkling effect and mucus secretion) exhibited delayed onset, suggesting intricate regulatory mechanisms underlying adaptability to environmental challenges; moreover, the wrinkling effect was consistently induced at higher concentrations, indicating greater sensitivity to the toxic effects of fluorene. With sublethal environmentally relevant concentrations-1.24 mg/l and 2.47 mg/L i.e., 10% and 20% 96 h, respectively-the antioxidant enzyme response (i.e., upregulation of SOD, CAT, and GST) with increasing fluorene concentration, revealing a nonlinear, hormetic response, suggested adaptive protection at lower doses but inhibition at higher concentrations. Histopathological examination indicated that higher fluorene concentrations caused cellular proliferation, inflammation, and severe tissue damage in the digestive tract and body wall. Molecular docking studies demonstrated robust interactions between fluorene and major stress biomarker enzymes, disrupting their functions and inducing oxidative stress. Interactions with cytochrome c oxidase suggested interference with cellular energy production. Generalized Read-Across (GenRA) analysis unveiled shared toxicity mechanisms among fluorene and its analogs, involving the formation of reactive epoxides and the influence of cytochrome P450 enzymes. The diverse functional groups of these analogs, particularly chlorine-containing compounds, were implicated in toxicity through lipid peroxidation and membrane damage. Adverse outcome pathways and broader consequences for aquatic ecosystem health are discussed.

A deoxygenation-switch-based red-emitting fluorogenic light-up probe for the detection of highly toxic free bilirubin in human blood serum.

Reaction-based chemical switches are attracting great interest due to their high selectivity, and their use has become a powerful technique for developing fluorogenic probes. Herein, a benzorhodol-derivative-attached N-oxide probe (DEBNox) has been designed as a new fluorogenic probe for the detection of the biologically toxic species bilirubin based on a deoxygenation switching mechanism. Upon reaction with added Fe3+, bilirubin produces Fe2+ ions in situ, which in turn promote a deoxygenation reaction with DEBNox to generate the corresponding high-red-fluorescence (λem: ∼623 nm) benzorhodol derivative (DEB). This type of Fe3+-mediated response helps the probe to act as a qualified turn on selective fluorescence sensor for bilirubin with a detection range as low as 33 nM. Moreover, the probe was successfully employed to detect free bilirubin in human blood serum specimens with acceptable accuracy and reliability. This DEBNox-based light-up strategy also facilitates the construction of reliable and highly sensitive assays based on a paper-based strategy, similar to pH-indicator paper, as is demonstrated here via bilirubin detection in real serum samples. These findings could be useful for developing powerful diagnostic tools for the detection of free bilirubin in the near further.

Investigation of house dust mite induced allergy using logistic regression in West Bengal, India.

BACKGROUND: The diagnosis of house dust mite (HDM) allergy based on Skin prick test (SPT) is not accurate, especially in lower risk cases. Our aim is to develop and validate a predictive model to diagnose the HDM allergic symptoms (urticaria, allergic rhinitis, asthma). METHODS: A forward-step logistic regression model was developed using a data set of 537 patients of West Bengal, India consisting of clinical variables (SPT based on 6 allergens of house dust and house dust mites, total IgE) and demographic characteristics (age, sex, house conditions). The output probability was estimated from the allergic symptoms shown by the patients. We finally prospectively validated a data set of 600 patients. RESULTS: The gradual inclusion of the variables increased the correlation between observed and predicted probabilities (correlation coefficient (r2) = 0.97). The model development using group-1 showed an accuracy rate of 99%, sensitivity and specificity of 99.7% and 88.6% respectively and the area under the receiver operating characteristics (ROC) curve (AUC) of 99%. The corresponding numbers for the validation of our model with group-2 were 87%, 95.6% and 66% and 86% respectively. The model predicted the probability of symptoms better than SPTs in combination (accuracy rate 0.76-0.80), especially in lower risk cases (probability< 0.8) that are highly difficult to diagnose. CONCLUSION: This is perhaps the first attempt to model the outcome of HDM allergy in terms of symptoms, which could open up an alternative but highly efficient way for accurate diagnosis of HDM allergy enhancing the efficiency of immunotherapy.